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BACKGROUND: As the ageing population grows, the demand for long-term care (LTC) services will rise, concurrently amplifying healthcare utilisation. This review aims to examine and consolidate information on LTC interventions that influence healthcare utilisation among older persons. METHODS: A scoping review was performed through a systematic search in PubMed, EBSCO CINAHL, EBM Reviews - Cochrane Database of Systematic Reviews, Embase, APA PsycInfo, EBM Reviews - Health Technology Assessment, and EBM Reviews - NHS Economic Evaluation Database. Systematic reviews with meta-analyses published between 1 January 2010 and 2 June 2022 among older persons aged 60 and above were included. The characteristics of LTC interventions were mapped to the World Health Organization (WHO) Healthy Ageing Framework. The effect sizes of healthcare utilisations for LTC interventions were recalculated using a random-effects model. The methodological quality was assessed with the AMSTAR-2 checklist, while the quality of evidence for each association was evaluated using GRADE. RESULTS: Thirty-seven meta-analyses were included. The most prominent domain of the healthy ageing framework was managing chronic conditions. One hundred twelve associations between various LTC interventions and healthcare utilisations were identified, with 22 associations impacting healthcare utilisation. Four interventions were supported by suggestive or convincing evidence. Preventive home visits were found to reduce hospital admission (OR: 0.73, 95% CI: 0.59, 0.91, p = 0.005), caregiver integration during discharge planning (OR: 0.68, 95% CI: 0.57, 0.81, p < 0.001), and continuity of care (OR: 0.76, 95% CI: 0.61, 0.95, p = 0.018) reduced hospital readmission, and perioperative geriatric interventions reduced the length of hospital stay (MD: -1.50, 95% CI: -2.24, -0.76, p < 0.001). None of the associations impacted emergency department visits, medication use, and primary care utilisations with convincing evidence. Most reviews received low methodological quality. CONCLUSION: The findings suggest that LTC interventions could benefit from transitioning to a community-based setting involving a multidisciplinary team, including carers. The spectrum of services should incorporate a comprehensive assessment to ensure continuous care.
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Cuidados a Largo Plazo , Aceptación de la Atención de Salud , Humanos , Cuidados a Largo Plazo/métodos , Cuidados a Largo Plazo/tendencias , Anciano , Anciano de 80 o más AñosRESUMEN
Normothermic Regional Perfusion, or NRP, is a method of donated organ reperfusion using cardiopulmonary bypass or a modified extracorporeal membrane oxygenation (ECMO) circuit after circulatory death while leaving organs in the dead donor's corpse. Despite its potential, several key ethical issues remain unaddressed by this technology.
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Confianza , Humanos , Perfusión , Oxigenación por Membrana Extracorpórea/ética , Preservación de Órganos/métodos , Preservación de Órganos/ética , Puente Cardiopulmonar/ética , Obtención de Tejidos y Órganos/éticaRESUMEN
EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.
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Enfermedades del Sistema Endocrino , Humanos , Enfermedades del Sistema Endocrino/terapia , Endocrinología/historia , Osteoporosis/terapiaRESUMEN
BACKGROUND AND AIMS: Analysis of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) have been proposed to increase the diagnostic yield of pH-impedance studies in reflux disease. However, routine use of these indices in clinical studies is yet to be established, particularly with PSPWi, which requires laborious manual analysis. Our study aimed to assess the utility of MNBI and PSPWi and their potential for future incorporation into clinical practice. METHODS: pH-impedance recordings from consecutive patients referred to the Motility Laboratory at Royal Adelaide Hospital for evaluation of gastro-oesophageal reflux disease (GORD) were prospectively collected and manually analysed. Baseline demographic characteristics, symptoms, acid exposure time (AET), number of reflux episodes, and MNBI and PSPWi were collected. RESULTS: Eighty-nine patients were included in the study (age 50 ± 17 years, 35 males). MNBI and PSPWi inversely correlated with AET (R = -0.678, P < 0.0001 and R = -0.460, P < 0.0001 respectively) and with reflux episodes (R = -0.391, P = 0.0002 and R = -0.305, P = 0.0037 respectively). In patients with a negative pH study, but with typical reflux symptoms, 4/30 (13%) had pathologic MNBI and PSPWi. There was a positive correlation between MNBI and PSPWi values (R = 0.525, P < 0.0001). Performing analysis of PSPWi was substantially more laborious than MNBI. CONCLUSION: MNBI and PSPWi are both useful adjuncts in the diagnosis of reflux disease, although in our cohort MNBI showed stronger correlation with AET with less time to analyse. The role of these indices remains to be further explored, particularly in patients with inconclusive AET and in those with positive compared to negative symptom association.
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Background: Elective surgeries were suspended during the national lockdown in March 2020 to curb the spread of the COVID-19 pandemic in Malaysia. We sought to evaluate the impact of the lockdown on cataract surgeries and suggest lessons for future outbreaks. Study design: We conducted an interrupted time series analysis to examine rates of cataract surgery before and during the lockdown. Methods: We used national cataract surgical data between 2015 and 2021 from the Malaysian Cataract Surgery Registry. Segmented regression with a seasonally adjusted Poisson model was used for the analysis. Stratified analyses were performed to establish whether the effect of the lockdown on cataract surgeries varied by hospital designation, type of cataract service, sex, and age groups. Results: Cataract surgeries began falling in March 2020 at the onset of the lockdown, reached a trough in April 2020, and subsequently increased but never recovered to pre-lockdown levels. Cataract surgical rates in December 2021 were still 43 % below the expected surgical volume, equivalent to 2513 lost cataract surgeries. There was no evidence of a differential effect of the lockdown between COVID-19 designated and non-COVID-19 designated hospitals. The relative decrease in cataract surgical rates appears to have been greatest in outreach services and in people 40 years and older. Conclusions: The lockdown caused an immediate reduction in cataract surgical rates to nearly half of its baseline rate. Despite its gradual recovery, further delays remain to be expected should there be no redistribution or increase in resources to support backlogs and incoming new cases.
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Alzheimer's disease (AD), due to its multifactorial nature and complex etiology, poses challenges for research, diagnosis, and treatment, and impacts millions worldwide. To address the need for minimally invasive, repeatable measures that aid in AD diagnosis and progression monitoring, studies leveraging RNAs associated with extracellular vesicles (EVs) in human biofluids have revealed AD-associated changes. However, the validation of AD biomarkers has suffered from the collection of samples from differing points in the disease time course or a lack of confirmed AD diagnoses. Here, we integrate clinical diagnosis and postmortem pathology data to form more accurate experimental groups and use small RNA sequencing to show that EVs from plasma can serve as a potential source of RNAs that reflect disease-related changes. Importantly, we demonstrated that these changes are identifiable in the EVs of preclinical patients, years before symptom manifestation, and that machine learning models based on differentially expressed RNAs can help predict disease conversion or progression. This research offers critical insight into early disease biomarkers and underscores the significance of accounting for disease progression and pathology in human AD studies.
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Enfermedad de Alzheimer , Vesículas Extracelulares , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Encéfalo/patología , Vesículas Extracelulares/patología , Diagnóstico Precoz , BiomarcadoresRESUMEN
INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.
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Esofagitis Eosinofílica , Inmunoglobulina G , Humanos , Esofagitis Eosinofílica/dietoterapia , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/sangre , Femenino , Masculino , Inmunoglobulina G/sangre , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Hipersensibilidad a los Alimentos/dietoterapia , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/sangre , Trastornos de Deglución/etiología , Trastornos de Deglución/dietoterapia , Esofagoscopía , Eosinófilos/inmunología , Adulto Joven , Dieta de EliminaciónRESUMEN
Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.
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Adenoma , Neoplasias Colorrectales , Animales , Humanos , Ratones , Adenoma/diagnóstico , Adenoma/terapia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Escherichia coli/genética , Estudios Prospectivos , Salicilatos , Método Doble CiegoRESUMEN
Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by âË»50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.
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Obesity is a disease with a major negative impact on human health. However, people with obesity may not perceive their weight to be a significant problem and less than half of patients with obesity are advised by their physicians to lose weight. The purpose of this review is to highlight the importance of managing overweight and obesity by discussing the adverse consequences and impact of obesity. In summary, obesity is strongly related to >50 medical conditions, with many of them having evidence from Mendelian randomisation studies to support causality. The clinical, social and economic burdens of obesity are considerable, with these burdens potentially impacting future generations as well. This review highlights the adverse health and economic consequences of obesity and the importance of an urgent and concerted effort towards the prevention and management of obesity to reduce the burden of obesity.
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Obesidad , Médicos , Humanos , SobrepesoRESUMEN
The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.
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The Fibrosis (FIB)-4 index is an established non-invasive test to detect liver fibrosis. Liver fibrosis is postulated to be one of the predictors of the risk of symptomatic Intracranial Haemorrhage (SICH) after intravenous tissue plasminogen activator (IV tPA) therapy, the mainstay of treatment following acute ischemic stroke (AIS). However, SICH is a feared complication of thrombolytic therapy. We aimed to evaluate the association of FIB-4 with outcomes of AIS after IV tPA. Consecutive AIS patients receiving IV tPA from 2006 to 2018 at a single stroke centre were studied in a retrospective cohort study. Multivariable adjusted logistic regression was performed to assess associations of FIB-4 with outcomes. The primary outcome was SICH, and secondary outcomes included functional independence (mRS of 0−2) and mortality measured at 90 days. Among 887 patients (median age: 67 (IQR: 57−77)), 342 had FIB-4 < 1.3 and 161 had FIB-4 > 2.67. A greater proportion of moderate to severe strokes (NIHSS ≥10) occurred in the FIB-4 > 2.67 group (n = 142, 88.8%) compared to the FIB-4 < 1.3 group (n = 208, 61.2%). Amongst the different stroke subtypes, median FIB-4 was highest in cardioembolic stroke (CES) compared to the 3 other non-CES stroke subtypes (1.90 (IQR: 1.41−2.69)). Following IV tPA, having FIB-4 > 2.67 was associated with an increased rate of SICH (adjusted OR: 4.09, 95% CI: 1.04−16.16, p = 0.045) and increased mortality (adjusted OR 3.05, 95% CI: 1.28−7.26, p = 0.012). Advanced liver fibrosis was associated with an increased rate of SICH and increased 90-day mortality after IV tPA. The FIB-4 score may be useful for prognostication after IV tPA.
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OBJECTIVES: To evaluate the humoral immunogenicity for 6 months after the two-dose coronavirus disease 2019 (COVID-19) mRNA vaccination in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs). METHODS: This monocentric observational study was conducted between August 2020 and March 2022. Humoral immunogenicity was assessed at 2-3 weeks after first vaccine dose and 1, 3 and 6 months after the second dose by the cPass™ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization antibody (nAb) assay. An inhibition signal of ≥30% defined the seroconversion threshold and the readings were calibrated against the World Health Organization International Standard for SARS-CoV-2 antibodies. RESULTS. ONE HUNDRED AND SIXTY-NINE: AYAs with cRDs were recruited [median age 16.8 years (interquartile range, IQR 14.7-19.5), 52% female, 72% Chinese]. JIA (58%) and SLE (18%) comprised the major diagnoses. After second vaccine dose, 99% seroconverted with a median nAb titre of 1779.8 IU/ml (IQR 882.8-2541.9), declining to 935.6 IU/ml (IQR 261.0-1514.9) and 683.2 IU/ml (IQR 163.5-1400.5) at the 3- and 6-month timepoints, respectively. The diagnosis of JIA [odds ratio (OR) 10.1, 95% CI 1.8-58.4, P = 0.010] and treatment with anti-TNF-α (aTNF) (OR 10.1, 95% CI 1.5-70.0, P = 0.019) were independently associated with a >50% drop of nAb titres at 6 months. Withholding MTX or MMF did not affect the vaccine response or decay rate. The COVID-19 breakthrough infection was estimated at 18.2 cases/1000 patient-months with no clinical risk factors identified. CONCLUSION: Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate.
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COVID-19 , Enfermedades Reumáticas , Niño , Adolescente , Femenino , Humanos , Adulto Joven , Masculino , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Inhibidores del Factor de Necrosis Tumoral , SARS-CoV-2 , Anticuerpos Antivirales , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
Contradicting evidence exists regarding the role of lipids in outcomes following intravenous (IV) thrombolysis with tissue plasminogen activator (tPA). Restricted cubic spline curves and adjusted logistic regression were used to evaluate associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio with poor functional outcome, symptomatic intracranial hemorrhage (SICH) and 90-day mortality, among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Quartile (Q) 1, Q2 and Q3 of HDL-C were associated with increased odds of poor functional outcome (adjusted odds ratio (adjOR) 1.66, 95% CI 1.06-2.60, p = 0.028, adjOR 1.63, 95% CI 1.05-2.53, p = 0.027, adjOR 1.56, 95% CI 1.01-2.44, p = 0.048) compared to Q4. Q2 and Q4 of non-HDL-C were associated with increased odds of SICH (adjOR 4.28, 95% CI 1.36-18.90, p = 0.025, adjOR 5.17, 95% CI 1.64-22.81, p = 0.011) compared to Q3. Q1 and Q2 of LDL-C was associated with increased odds of mortality (adjOR 2.57, 95% CI 1.27-5.57, p = 0.011 and adjOR 2.28, 95% CI 1.10-5.02, p = 0.032) compared to Q3. In AIS patients who received IV tPA, low LDL-C was associated with increased odds of mortality while HDL-C may be protective against poor functional outcome.
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Background: Food texture can moderate eating rate and ad libitum energy intake. Many foods are combined with condiments when consumed and the texture and eating properties differ considerably between condiments and carrier foods. Little is known about how combinations of textures impact oral processing or whether these differences are affected by individual eating-styles. Objective: We investigated the impact of texture parameters (unit size, thickness, hardness and lubrication) on oral processing behaviours for carrots and rice-crackers, and tested whether these behaviours differ between 'faster' and 'slower' eaters. Method: Seventy participants (34 males, 26.0 ± 5.4 years, BMI = 21.5 ± 1.7 kg m-2) consumed 24 weight-matched carrot samples varying in unit size (large/medium/small), thickness (thick/thin), hardness (hard/soft) and lubrication (with/without mayonnaise). In a second step, participants consumed 8 weight-matched cracker samples varying in unit size (large/small), hardness (hard/soft) and lubrication (with/without mayonnaise). Sample consumption was video-recorded for post hoc behavioural annotation to derive specific oral processing behaviours. Participants were divided into 'faster' or 'slower' eater groups using a post hoc median split based on eating rate of raw carrot. Results: Across texture parameters, hardness had the largest influence (p < 0.001) on eating rate for both carrots and crackers. The independent texture differences for carrot ranked from most to least impact on eating rate was hardness > thickness > lubrication > unit size. For crackers, the rank order of eating rate was hardness > lubrication > unit size. Harder carrot samples with decreased unit size and reduced thickness combined had a larger synergistic effect in reducing eating rate (p < 0.001) than manipulation of any single texture parameter alone. Reducing the unit size of crackers while increasing hardness without lubrication combined (p = 0.015) to produce the largest reduction in eating rate. There were no significant differences between fast and slow eaters on their oral processing behaviours across texture manipulations. Conclusions: Combinations of texture manipulations have the largest impact in moderating oral processing behaviours, and this is consistent across 'faster' and 'slower' eaters. Changing food-texture presents an effective strategy to guide reformulation of product sensory properties to better regulate eating rate and energy intake, regardless of an individual's natural eating-style.
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Ingestión de Energía , Conducta Alimentaria , Condimentos , Ingestión de Alimentos/fisiología , Alimentos , Preferencias Alimentarias , Humanos , MasculinoRESUMEN
Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand-receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.
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Epilepsia , Transcriptoma , Encéfalo/patología , Epilepsia/genética , Epítopos , Humanos , Microglía/patologíaRESUMEN
While there is evidence that mental health problems are more prevalent in people with borderline intellectual functioning (BIF) compared to the general population, it is not known to what extent this has varied or changed over time and whether there have been changes in access to services. This paper compares the prevalence rates of psychiatric disorders and monitors trends in treatment and services in this population compared to the general population. We conducted secondary analysis on the Adult Psychiatric Morbidity Surveys carried out in England in 2000, 2007 and 2014. The total sample analysed included 21,796 participants, with 12.8% of individuals identified with BIF (n = 2786). Regression models were used to examine trends in psychiatric disorders, treatment and service use across the three datasets. People with BIF had significantly higher odds of developing mood and anxiety disorders, psychosis, drug dependence and suicidal behaviour than the general population, increasing at each subsequent timepoint. They received significantly more pharmacological treatments than the general population but have had increasingly more access to general practitioners, community care and daycare services over time. This study shows increasing prevalence rates of several mental disorders in people with BIF. Access to day-care, community care and healthcare services has increased over time for this group but not formal psychiatric care. These changes over time underline some of the problems this population faces, emphasizing a need to recognize that this is a population often overlooked in research and clinical practice.
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Discapacidad Intelectual , Discapacidades para el Aprendizaje , Trastornos Mentales , Trastornos Psicóticos , Adulto , Trastornos de Ansiedad , Estudios Transversales , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Trastornos Mentales/terapia , Prevalencia , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/terapiaRESUMEN
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of antidiabetic medications with a favourable cardiovascular, renal and overall safety profile. Given the limited treatment options available for neurological disorders, it is important to determine whether the pleiotropic effects of SGLT2i can be utilised in their prevention and management. Methods: All articles published before 20 March 2021 were systematically searched in MEDLINE, EMBASE, Scopus, Web of Science, APA PsycINFO and ClinicalTrials.gov. Overall, 1395 titles were screened, ultimately resulting in 160 articles being included in the qualitative analysis. Screening and data extraction were conducted by two independent authors and studies were excluded if they were not an original research study. Findings: Of the 160 studies, 134 addressed stroke, 19 cognitive impairment, 4 epilepsy and 4 movement disorders, encompassing a range from systematic reviews and randomised controlled trials to bioinformatic and animal studies. Most animal studies demonstrated significant improvements in behavioural and neurological deficits, which were reflected in beneficial changes in neurovascular units, synaptogenesis, neurotransmitter levels and target receptors' docking energies. The evidence from the minority clinical literature was conflicting and many studies did not reach statistical significance. Interpretation: SGLT2i may exert neurological benefits through three mechanisms: reduction in cardiovascular risk factors, augmentation of ketogenesis and anti-inflammatory pathways. Most clinical studies were observational, meaning that a causal relationship could not be established, while randomised controlled trials were heterogeneous and powered to detect cardiovascular or renal outcomes. We suggest that a longitudinal study should be conducted and specifically powered to detect neurological outcomes.
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The development of the CRISPR gene editing technique has been hyped as a technique that could fundamentally change scientific research and its clinical application. Unrecognized is the fact that it joins other technologies that have tried and failed under the same discourse of scientific hype. These technologies, like gene therapy and stem cell research, have moved quickly passed basic research into clinical application with dire consequences. Before hastily moving to clinical applications, it is necessary to consider basic research and determine how CRISPR/Cas systems should be applied. In the case of single gene diseases, that application is expected to have positive impacts, but as we shift to more complex diseases, the impact could be unintentionally negative. In the context of common disabilities, the level of genetic complexity may render this technology useless but potentially toxic, aggravating a social discourse that devalues those with disabilities. This paper intends to define the issues related to disability that are associated with using the CRIPSR/Cas system in basic research. It also aims to provide a decision tree to help determine whether the technology should be utilized or if alternative approaches beyond scientific research could lead to a better use of limited funding resources.